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Affinity chromatography by m-aminophenylboronic acid has been proposed for routine measurement of glycated albumin. We assayed glycated and non-glycated fractions of serum albumin (HSA) eluted by affinity chromatography columns by both a specific RIA method for the human serum albumin (HSA) and by a colorimetric method. Sixteen diabetic patients presented a significantly higher percentage of glycated-HSA than 7 control subjects with both methods, and a strong correlation was found between the values obtained with the two methods. RIA was able to detect a significant concentration of glycated-HSA in all normal subjects, while the colorimetric method was not. The accuracy of separation between the glycated and non-glycated fractions of albumin was tested using [14C]glucose as tracer. When [14C]glycated-HSA purified by Sephadex G25 filtration was chromatographed using the m-aminophenylboronic acid, only 5.3% of the total 14C-radioactivity present in the solution was recovered in the bound fraction, while 44.0% was eluted in non-protein-bound fraction and 54.7% was retained in the column. Our findings confirm that affinity chromatography by m-aminophenylboronic acid can be a useful tool in the monitoring of short glycemic control of diabetic patients. Our data also indicate that the affinity chromatography with m-aminophenylboronic acid does not accurately discriminate between glycated and non-glycated fraction of HSA.

We randomly administered thyrotropin-releasing hormone (200 micrograms, as an i.v. bolus) or control saline (in isovolumic amount) to 30 male diabetic subjects (23 IDDM, 7 NIDDM) in fair metabolic control (HbA1 9.7 +/- 0.3%, means +/- SEM) and to 12 healthy male controls on two different mornings. While GH in the basal state was similar in IDDM, NIDDM and normal subjects, TRH administration evoked a significant GH release only in a single IDDM individual. The only GH-responder to TRH was a newly-diagnosed (two weeks) IDDM patient, still with a high glycated hemoglobin level (HbA1 11.1%), despite normal plasma glucose levels. Saline infusion did not affect GH concentrations either in normals or in diabetics. Exaggerated GH responses to TRH are uncommon in diabetic patients in good metabolic conditions.

Low doses of metformin (500 mg twice daily) were administered to 20 diabetic patients, combined with the original sulfonylurea treatment which had become ineffective even at full dosage. After 1 and 5 weeks, the effects of the drug on glycemic control, blood intermediate metabolites and monocyte insulin receptors were monitored. Metformin clearly improved glycemic control by reducing both fasting blood glucose from 189.88 +/- 21.11 mg/dl to 131.12 +/- 16.02 mg/dl after 1 week and to 130.11 +/- 13.29 mg/dl after 5 weeks (p less than 0.025 both after 1 and 5 weeks); the diurnal blood glucose average fell from 235.33 +/- 24.11 mg/dl to 174.66 +/- 23.45 mg/dl (p less than 0.0025) after 1 week and to 177.65 +/- 21.71 mg/dl (p less than 0.0005) after 5 weeks. Consequently both blood glycosylated hemoglobin (p = n.s. after 1 week, p less than 0.025 after 5 weeks) and serum fructosamine (p less than 0.0025 after both 1 and 5 weeks) also decreased after metformin treatment. No change in plasma insulin and C-peptide levels was reported and no modification in diurnal rhythms of blood lactate, pyruvate, alanine glycerol and beta-OH-butyrate was detected at any time during metformin treatment. All the changes documented in the binding values were already complete at the end of the first week; insulin binding to monocytes increased slightly but significantly (p less than 0.05) and the number of receptors per cell rose (p less than 0.05) but could not be correlated to any index of glycemic control. These data suggest that the antidiabetic action of metformin is neither related to its lactate-increasing activity nor does it depend upon its inducing an increase in insulin binding values. This metformin-related hypoglycemic effect might be the result, at least in part, of a reduced oxidative phosphorylation without inhibition of hepatic gluconeogenesis and/or of decreased hepatic glucose output. Moreover, our data are also consistent with the hypothesis that metformin might affect insulin action at a post-receptor level.

The effects of individual teaching imparted during routine diabetologic counselling on the knowledge concerning diabetes and metabolic control, were assessed in 42 outpatients (28 IDDM; 14 NIDDM), attending the diabetic clinic (study group, SG). We evaluated the outcome of a multiple-choice questionnaire and fasting blood glucose (FBG), 24-h urine glucose (UG), mean regulation index (MRI) and glycated hemoglobin (HbA1), before and 60 days after providing information about diet (D), physical exercise (E) and hypoglycemic drugs (HD) or insulin therapy (IT). Results were compared with those obtained in a group of 57 age- and sex-matched patients (36 IDDM; 21 NIDDM) who did not receive individual teaching (control group, CG). Knowledge concerning diabetes at the second evaluation was significantly higher (p less than 0.001) in SG than in CG for D and IT, although an improvement was observed in all items. SG patients showed a significant improvement of knowledge (p less than 0.05) for D, a not significant improvement for HD and IT and no change for E. No change was observed for HbA1, MRI and UG, while a significant decrease (p less than 0.05) was observed for FBG in SG. At the second evaluation, FBG of SG patients was significantly lower (p less than 0.05) than that of CG patients. Our results go to show that individual teaching can improve the level of knowledge of patients without affecting metabolic control. Individual teaching during routine diabetologic counselling represents in our opinion an effective and economic educational model.

We investigated the frequency of microalbuminuria (albumin excretion rate, AER greater than 15 micrograms/min) ('overnight' urine collection and radioimmunological evaluation) and its relation to retinopathy (assessed by fluorangiography) in 113 type I (insulin-dependent) diabetic subjects (aged 31 +/- 13 years; diabetes duration 11 +/- 7 years), all Albustix-negative. Sixty eight patients (60.2%) were free of retinal lesions, 31 (27.4%) had background retinopathy and 14 (12.4%) had proliferative retinopathy. Microalbuminuria was found in 25 patients (22%). Fifteen patients (13%) showed both retinopathy and microalbuminuria. Fifteen % (10/68) of the patients with no retinopathy and sixteen % (5/31) of those with background retinal lesions had microalbuminuria, while 29% (4/14) of the patients with proliferative retinopathy were normoalbuminuric. Among the 29 patients with diabetes for less than five years, 1 had retinopathy and 4 had microalbuminuria. Out of 15 patients with both retinopathy and microalbuminuria, 13 (87%) had had diabetes for more than 10 years. Diabetic retinopathy is more frequent than microalbuminuria (40 vs 22%). Although the linkage between retinopathy and microalbuminuria is weak, after ten years of diabetes the two complications may frequently coincide.

A patient with recurrent hypoglycemic episodes associated with a leiomyosarcoma of the small bowel is described. Fasting plasma insulin levels were consistently low and a subnormal insulin response to provocative stimuli (oral glucose and i.v. glucagon) was shown. After removal of the tumor, hypoglycemic episodes disappeared, fasting plasma insulin concentrations rose to normal values and insulin response to both OGTT and glucagon test was markedly enhanced. The possible mechanisms responsible for the hypoglycemia and the causes of subnormal insulin response to provocative stimuli are discussed.

Since insulin modulates key enzymes of lipid metabolism, different biological activities of biosynthetic human insulin (BHI) and conventional insulins might induce different plasma lipid and apolipoprotein patterns in diabetic patients chronically treated with the former or the latter insulin preparation. In this study we have evaluated the effects of 3 months of therapy with BHI on plasma lipid and apolipoprotein concentrations in a group of type I diabetics previously treated with insulin of animal origin and the results have been compared with those from diabetics maintained on conventional insulin therapy. In the latter, no change occurred in the clinical and metabolic parameters. Patients transferred to BHI showed lower HDL-cholesterol and HDL3-cholesterol levels at 30 days from the beginning of BHI treatment, and both parameters returned to, and were maintained the basal values at subsequent controls. Total cholesterol, HDL2-cholesterol, triglycerides, apolipoproteins AI, AII and B remained substantially constant throughout the study. Glycometabolic control, which was evaluated by fasting plasma glucose and glycosylated hemoglobin, exhibited a transient, moderate deterioration at the 30-day control, and returned to basal level in the following weeks. No major change was noted as far as daily insulin dosage and relative body weight were concerned. Thus, long-term BHI treatment of type I diabetics does not cause any major change in plasma lipid and apolipoprotein patterns in comparison with animal insulin therapy, so that the validity of using BHI in the treatment of type I diabetes is confirmed.

A pasta containing 10% guar-flour was successfully prepared and administered to ten obese women in a seven-day experimental design which included: a control meal (day 1) containing alimentary wheat-pasta, a first guar-pasta meal (day 2), to assess the acute effects of guar-pasta, a second guar-pasta meal (day 7), performed after four days of a weight-maintenance diet containing one guar-pasta meal per day. Compared to wheat-pasta, guar-pasta significantly lowered glucose and insulin response, as well as fasting total cholesterol. Moreover, it had excellent palatability and no gastrointestinal side-effects.

The relationships between free insulin and various clinical and metabolic parameters in insulin-treated diabetic patients are still not clear, possibly because of the technical difficulties in measuring free insulin. Recently, it has been demonstrated that in the presence of insulin antibodies only immediate centrifugation of blood and extraction of insulin antibodies provide an accurate evaluation of in vivo free insulin concentrations. In this study we evaluated the relationships between free and bound insulin levels, insulin antibodies, metabolic control and insulin requirement in 38 insulin-treated diabetic patients, in whom plasma free insulin was assayed in immediately processed samples. The main findings of our study are as follows. Free insulin concentrations ranged from 2.5 to 54 microU/ml; no difference was found between males and females; the unbound hormone level was inversely correlated to fasting plasma glucose (p less than 0.01) and HbA1c (p less than 0.02); a positive correlation was shown between free insulin and daily insulin dose; finally, free insulin concentrations were not correlated with insulin antibody binding.

In order to evaluate if in insulin-dependent diabetes lipid and apolipoprotein levels are differently affected by metabolic control in men and women, we measured the concentrations of fasting plasma glucose, mean plasma glucose, glycosylated hemoglobin, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and apolipoproteins A and B in 94 sex matched patients. Diabetic men and women were strictly comparable as far as age, relative body weight and metabolic control were concerned. In women, total and LDL cholesterol, triglycerides and apolipoprotein A correlated positively with HbA1 but not with fasting and mean plasma glucose. In men, no correlation between metabolic control and lipid and apolipoprotein levels was found. We conclude that, in diabetic women, the degree of metabolic control may affect the concentrations of plasma lipids, thus explaining, at least in part, the increased risk for coronary atherosclerosis in these patients.

Alternative medications for hyperlipidemia management have been continuously searched for above all because currently employed drugs appear not to be effective or are poorly tolerated. Fibers, such as guar-gum, seem to be able to reduce cholesterol levels, but their extensive and long-term use is beset by the high incidence of gastrointestinal side-effects. In this study the administration of guar-enriched pasta has proved to reduce fasting and post-prandial cholesterol levels significantly in 15 obese normocholesterolemic women (5 diabetics and 10 non-diabetics). The women reported good palatableness of guar-pasta without any side-effects.